Adrenal insufficiency

In 1855, Thomas Addison identified a clinical syndrome characterized by wasting and hyperpigmentation as the result of adrenal gland destruction (1). This landmark observation paved the way for progress in understanding and treating adrenal insufficiency, with the introduction of adrenal extracts for treatment of Addison’s disease by the groups of Hartman and Pfiffner in 1929. However, long-term survival of patients with adrenal insufficiency only became possible after the seminal work of Edward Kendall, Philip Hench, and Tadeus Reichstein on the characterization and therapeutic use of cortisone. In 1946, Lewis Sarrett, a Merck scientist, achieved a partial synthesis of cortisone, which marked the beginning of industrial-scale production of cortisone. In 1948, in a fundamental clinical experiment at the Mayo Clinic, the first patient with Addison’s received intravenous injections of Kendall’s Compound E, cortisone, resulting in ‘notable improvement of his condition’. This was followed by the groundbreaking trials on the use of cortisone in rheumatoid arthritis yielding unanticipated clinical improvements, which quickly led to the labelling of cortisone as ‘the wonder drug’. In November 1950, cortisone was made available to all physicians in the USA, a rapid translational development process, which culminated in the award of the 1950 Nobel Prize in Medicine to Kendall, Hench, and Reichstein. This progress reached other countries with variable delay and widespread availability of cortisone in the UK was achieved by joint efforts of Glaxo and the Medical Research Council. Though almost 150 years have passed since Addison’s landmark observations and 60 years since the introduction of life-saving cortisone, there are still advances and challenges in the management of adrenal insufficiency, summarized in this chapter.